Renal Denervation for Uncontrolled and Resistant Hypertension: Systematic Review and Network Meta-Analysis of Randomized Trials

Abstract

Comparative efficacy and safety of renal denervation (RDN) interventions for uncontrolled (UH) and resistant hypertension (RH) is unknown. We assessed the comparative efficacy and safety of existing RDN interventions for UH and RH. Six search engines were searched up to 1 May 2020. Primary outcomes were mean 24-h ambulatory and office systolic blood pressure (SBP). Secondary outcomes were mean 24-h ambulatory and office diastolic blood pressure (DBP), clinical outcomes, and serious adverse events. Frequentist random-effects network meta-analyses were used to evaluate effects of RDN interventions. Twenty randomized controlled trials (RCTs) (n = 2152) were included, 15 in RH (n = 1544) and five in UH (n = 608). Intervention arms included radiofrequency (RF) in main renal artery (MRA) (n = 10), RF in MRA and branches (n = 4), RF in MRA+ antihypertensive therapy (AHT) (n = 5), ultrasound (US) in MRA (n = 3), sham (n = 8), and AHT (n = 9). RF in MRA and branches ranked as the best treatment to reduce 24-h ambulatory, daytime, and nighttime SBP and DBP versus other interventions (p-scores: 0.83 to 0.97); significant blood pressure effects were found versus sham or AHT. RF in MRA+AHT was the best treatment to reduce office SBP and DBP (p-scores: 0.84 and 0.90, respectively). RF in MRA and branches was the most efficacious versus other interventions to reduce 24-h ambulatory SBP and DBP in UH or RH.

Renal denervation in the antihypertensive arsenal – knowns and known unknowns

“…RDN will likely offer a similar effect on BP among patients with resistant hypertension to those with untreated hypertension but the magnitude of BP lowering is not as large as once perceived (24 h systolic BP reduction of 1–10 mmHg, office systolic BP reduction of 7–10 mmHg) [105]. This reduction will be relatively minute among those with severe resistant hypertension with baseline systolic BP of 180 mmHg or above despite 5 or more antihypertensive drugs as other factors such as secondary causes of hypertension (primary aldosteronism, obstructive sleep apnea) or unrecognized medication nonadherence are likely to have a larger role on BP control which cannot be modified by RDN.…”

“…Several meta-analyses and systemic reviews that have been conducted to determine effects of RDN in patients with resistant hypertension yielded conflicting results. While some showed no benefit on office or 24-h ABP [24,103,104], more recent meta-analysis which includes newer trials such as RADIOSOUND and RADIANCE-HTN TRIO showed a significant reduction in 24-h ABP, particularly when RDN was conducted in both main renal arteries and the side branches [105]. The heterogeneity in the outcomes among these trials and meta-analyses are likely related to adherence to antihypertensive medications which are typically low in patients with apparently resistant hypertension [106][107][108][109].…”

Devices for the treatment of arterial hypertension

“…The meta-analysis of Stavropoulos et al did not show a reduction in pressure after the use of the first generation of renal denervation devices, while the use of the second generation of these devices resulted in a significant decrease in pressure compared to sham procedures [35]. The greatest drop in blood pressure was observed in patients whose renal denervation was related to the main renal artery and its branches [34]. Irrespective of the pressure reduction, renal denervation reduces the variability of blood pressure, which was confirmed by the meta-analysis of Vogiaztzakis et al [36].…”

“…Numerous metaanalyses assessing the effectiveness of renal denervation for reducing hypertension have already been published. Most of them have shown success, [30][31][32][33][34][35][36] but not all [37].…”

Renal denervation for atrial fibrillation: a comprehensive updated systematic review and meta-analysis

“…This highlights the existence of a more complex pathophysiological mechanism that defies current therapeutic regimens [ 5 ]. More recently, the development of endovascular catheters has allowed for easy access to the renal artery lumen to specifically ablate renal nerves and hence multiple trials were executed over the last decade to carefully examine the effect on renal sympathetic outflow and the downstream effect on blood pressure [ 6 ]. The benefits as such of renal denervation (RDN) were further reiterated in multiple trials and a recent network meta-analysis of 20 trials ( n = 2152) showed that RDN of main renal artery branches in addition to antihypertensive therapy is most effective in reducing office blood pressure and that RDN using this approach was superior in reducing ambulatory blood pressure compared to sham or antihypertensive therapy alone [ 6 ].…”